POS0664 RADIOGRAPHIC CHANGE IN PATIENTS WITH RHEUMATOID ARTHRITIS AND ESTIMATED BASELINE YEARLY PROGRESSION ≥5 OR &lt;5: POST HOC ANALYSIS OF TWO PHASE 3 TRIALS OF FILGOTINIB
Authors: Y. Tanaka, T. Atsumi, D. Aletaha, R. B. M. Landewé, B. Bartok, A. Pechonkina, Z. Yin, L. Han, K. Emoto, S. Kano, V. Rajendran, T. Takeuchi
Journal: Annals of the Rheumatic Diseases (2022)

Background In some patients (pts) with rheumatoid arthritis (RA), especially those with joint damage early in the disease, first-line methotrexate (MTX) treatment may not suffice to prevent further rapid radiographic progression (RRP). 1 In FINCH 1 ( NCT02889796 ), filgotinib 200 mg (FIL200) and 100 mg (FIL100) reduced change in modified total Sharp score (mTSS) vs placebo (PBO) in pts with RA and inadequate response to MTX (MTX-IR). 2 In FINCH 3 ( NCT02886728 ), FIL200 and FIL100 reduced change in mTSS vs MTX monotherapy (MTX mono) in MTX-naïve pts. 3 Objectives To evaluate, via post hoc analysis of 2 trials, filgotinib’s effects on radiographic progression vs MTX mono in pts with estimated baseline (BL) yearly progression ≥5 or &lt;5 mTSS units/year. Methods The double-blind 52-week (W) FINCH 1 study randomised MTX-IR pts with moderate–severe active RA to FIL200 or FIL100, subcutaneous adalimumab (ADA) 40 mg, or PBO; at W24, PBO pts were rerandomised blinded to FIL200 or FIL100; all took stable background MTX. 2 In FINCH 3, MTX-naïve pts were randomised, blinded, to FIL200 + MTX, FIL100 + MTX, FIL200 alone, or MTX mono for up to W52. 3 This analysis examined subgroups by estimated BL yearly progression (BL mTSS/duration in years of RA diagnosis), based on ≥5 or &lt;5 mTSS units/year, 4 a threshold commonly used to define RRP. We assessed effects of filgotinib vs ADA or PBO in mTSS change from BL (CFB) at W24/W52 (using a mixed model for repeated measures) and percentages with no W24 progression (mTSS change ≤0, ≤0.5, ≤smallest detectable change [SDC], using Fisher’s exact test). Results At BL, 558/1755 MTX-IR and 787/1249 MTX-naïve pts had BL estimated yearly progression ≥5. Median mTSS in pts with BL yearly progression ≥5 and &lt;5 was 53.25 vs 5.00 respectively in the MTX-IR trial and 6.00 vs 2.50 in the MTX-naïve trial. At W24, the mTSS CFB in pts with BL yearly progression ≥5 and &lt;5 was 0.84 and 0.22 in MTX-IR pts taking PBO + MTX, and 0.67 and 0.25 in MTX-naïve pts taking MTX mono. At W52, in pts with BL yearly progression ≥5, FIL200 + MTX reduced mTSS change vs PBO + MTX in the MTX-IR trial and vs MTX mono in the MTX-naïve trial (Figure 1). At W24, among pts with estimated BL yearly progression ≥5, FIL200 + MTX increased odds of no progression (≤0.5 or ≤0) vs PBO + MTX in MTX-IR pts and vs MTX mono in MTX-naïve pts (Table 1). Table 1. Ratio of no radiographic progression at W24 FINCH 1: MTX-IR FIL200 + MTX FIL100 + MTX ADA + MTX PBO + MTX BL yearly progression ≥5(n = 138) &lt;5(n = 267) ≥5(n = 139) &lt;5(n = 265) ≥5(n = 91) &lt;5(n = 180) ≥5(n = 101) &lt;5(n = 250) % with no progression (≤0.5) 87.7 97.0 88.5 92.5 87.9 93.9 76.2 91.6 OR 2.22* 2.97* 2.40* 1.12 † † † † % with no progression (≤0) 80.4 91.8 81.3 88.3 80.2 89.4 67.3 86.4 OR 2.00* 1.75 2.11* 1.19 † † † † % with no progression (≤SDC [1.36]) 91.3 98.1 92.1 96.6 92.3 95.6 81.2 94.0 OR 2.43* 3.35* 2.70* 1.82 † † † † FINCH 3: MTX-naïve FIL200 + MTX FIL100 + MTX FIL200 mono MTX BL yearly progression ≥5 &lt;5 ≥5 &lt;5 ≥5 &lt;5 ≥5 &lt;5 (n = 221) (n = 134) (n = 121) (n = 63) (n = 115) (n = 58) (n = 224) (n = 132) % with no progression (≤0.5) 86.9 94.0 83.5 93.7 89.6 89.7 78.6 87.9 OR 1.81* 2.17 1.38 2.03 2.34* 1.20 † † % with no progression (≤0) 78.7 83.6 72.7 84.1 80.0 87.9 67.9 80.3 OR 1.75* 1.25 1.26 1.3 1.89* 1.79 † † % with no progression (≤SDC [1.53]) 93.7 97.8 91.7 96.8 95.7 96.6 89.3 95.5 OR 1.77 2.08 1.33 1.45 2.64 1.33 † † MTX-IR ORs are FIL vs PBO + MTX; MTX-naïve are FIL vs MTX. *Nominal P &lt;.05. †Not applicable. ADA, adalimumab; FIL, filgotinib; IR, inadequate response; mTSS, modified total Sharp score; MTX, methotrexate; OR, odds ratio; SDC, smallest detectable change; W, week. Conclusion These data suggest filgotinib’s inhibition of radiographic progression was numerically greater than MTX monotherapy in RA pts with high estimated BL yearly progression. In those with a more moderate estimated rate of progression, filgotinib suppressed progression comparably to ADA and/or MTX. References [1]Smolen J et al. Ann Rheum Dis 2018;77:1566–1572. [2]Combe B et al. Ann Rheum Dis 2021;80:848–858. [3]Westhovens R et al. Ann Rheum Dis 2021;80:727–738. [4]Vastesaeger N et al. Rheumatology . 2009;48:1114–1121. Acknowledgements This study was funded by Gilead Sciences, Inc., Foster City, CA. Medical writing support was provided by Rob Coover, MPH, of AlphaScientia, LLC, San Francisco, CA; and funded by Gilead Sciences, Inc., Foster City, CA. Funding for this analysis was provided by Gilead Sciences, Inc. The sponsors participated in the planning, execution, and interpretation of the research. Disclosure of Interests Yoshiya Tanaka Speakers bureau: AbbVie, Amgen, Astellas, AstraZeneca, Behringer-Ingelheim, Bristol-Myers Squibb, Chugai, Eisai, Eli Lilly, Gilead, Mitsubishi-Tanabe, and YL Biologics, Grant/research support from: AbbVie, Asahi-Kasei, Boehringer-Ingelheim, Chugai, Corrona, Daiichi Sankyo, Eisai, Kowa, Mitsubishi-Tanabe, and Takeda, Tatsuya Atsumi Paid instructor for: Gilead Sciences, Inc.; Mitsubishi Tanabe; Chugai; Astellas Pharma; Takeda; Pfizer; AbbVie: Eisai; Daiichi Sankyo; Bristol-Myers Squibb; UCB Japan Co. Ltd.; Eli Lilly Japan K.K., Otsuka Pharmaceutical Co., Ltd.; and Alexion Inc., Grant/research support from: Gilead Sciences, Inc.; Mitsubishi Tanabe; Chugai; Astellas Pharma; Takeda; Pfizer; AbbVie: Eisai; Daiichi Sankyo; Bristol-Myers Squibb; UCB Japan Co. Ltd.; Eli Lilly Japan K.K., Otsuka Pharmaceutical Co., Ltd.; and Alexion Inc., Daniel Aletaha Speakers bureau: AbbVie; Amgen; Celgene; Eli Lilly; Medac; Merck; Novartis; Pfizer; Roche; Sandoz; and Sanofi/Genzyme; Bristol-Myers Squibb, Merck Sharp &amp; Dohme, and UCB, Consultant of: Janssen; AbbVie; Amgen; Celgene; Eli Lilly; Medac; Merck; Novartis; Pfizer; Roche; Sandoz; and Sanofi/Genzyme, Grant/research support from: AbbVie, Merck Sharp &amp; Dohme, Novartis, and Roche, Robert B.M. Landewé Paid instructor for: AbbVie, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Galapagos NV, Novartis, Pfizer, and UCB, Consultant of: AbbVie, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Galapagos NV, Novartis, Pfizer, and UCB, Beatrix Bartok Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc, Alena Pechonkina Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Zhaoyu Yin Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Ling Han Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences, Inc., Kahaku Emoto Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences K.K., Shungo Kano Shareholder of: Gilead Sciences, Inc., Employee of: Gilead Sciences K.K., Vijay Rajendran Employee of: Galapagos BV, Tsutomu Takeuchi Speakers bureau: AbbVie, Ayumi Pharmaceutical Corporation, Bristol-Myers Squibb, Chugai, Daiichi Sankyo, Dainippon Sumitomo Eisai, Eli Lilly Japan, Mitsubishi-Tanabe, Novartis, Pfizer Japan, Sanofi, and Gilead Sciences, Inc., Consultant of: Astellas, Chugai, and Eli Lilly Japan, Grant/research support from: AbbVie, Asahi Kasei, Astellas, Chugai, Daiichi Sankyo, Eisai, Mitsubishi-Tanabe, Shionogi, Takeda, and UCB Japan